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Revista Brasileira de Hematologia e Hemoterapia

Print version ISSN 1516-8484

Rev. Bras. Hematol. Hemoter. vol.34 no.5 São Paulo  2012 



The utility of multiparametric flow cytometry for the detection of minimal residual disease in acute lymphoblastic leukemia



Fernanda Gonçalves Pereira Cunha; Felipe Franco da Rocha; Irene Gyongyver H. Lorand-Metze

Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brazil

Corresponding author



The quantification of the amount of minimal residual disease (MRD) in the bone marrow (BM) of patients with acute lymphoblastic leukemia (ALL) at several points of the treatment of the disease has proven to be an important independent predictor of treatment outcome(1-5). More recently, treatment protocols have been designed to adjust chemotherapy according to the presence or absence of MRD on day 8 or 15 of the induction therapy and at the end of induction (day 29) in order to deliver sufficient chemotherapy to cure the patient and minimize acute and long-term side effects. However, this approach is only justified in controlled clinical studies.

Flow cytometry, an essential component of the diagnostic work-up in ALL, is used to determine the cell lineage of leukemic blasts, to quantify antigen expression and to detect aberrant antigen expressions. These data are essential for the detection of abnormal cell populations in the BM in the study of MRD. It has been shown that leukemic blasts may be distinguished from normal lymphoid precursors in up to 87% of ALL cases. Moreover, if the technique is well standardized, it is able to detect one abnormal cell among 10,000 to 100,000 normal BM cells(3).

Several different panels of antibody combinations have been described with some also considering the cost-effectiveness and simplicity(1,5). However, combinations of at least four colors are essential to give reliable results.

The following figure presents the analysis of a case of B-cell ALL. The abnormal blasts may be distinguished from the normal ones by their deficient and variable expression of CD45 (Figure 1).



1. Patkar N, Abu Alex AA, Bargavi B, Ahmed R, Abraham A, George B, et al. Standardizing minimal residual disease by flow cytometry for precursor b lineage acute lymphoblastic leukemia in a developing country. Cytometry B Clin Cytom. 2012;82(4):252-8.         [ Links ]

2. Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M, et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011;117(23):6267-76.         [ Links ]

3. Campana D. Minimal residual disease in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2010;2010:7-12.         [ Links ]

4. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, Linda S, Martin PL, Pullen DJ, Viswanatha D, Willman CL, Winick N, Camitta BM; Children's Oncology Group. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008;111(12):5477-85         [ Links ]

5. Delbuono E, Maekawa YH, Latorre MR, Seber A, Petrilli AS, Braga JAP, Lee ML. Simplified flow cytometric assay to detect minimal residual disease in childhood with acute lymphoblastic leukemia. Rev Bras Hematol Hemoter. 2008;30(4):281-6.         [ Links ]



Corresponding author:
Rodolfo Delfini Cançado
Irene Lorand-Metze Centro de Hematologia e Hemoterapia de Campinas, Universidade Estadual de Campinas- Unicamp
Rua Carlos Chagas, 450 - Cidade Universitária "Prof. Zeferino Vaz", Distrito de Barão Geraldo
13083-878, Campinas, SP, Brazil
Phone: 55 19-3521 8740

Submitted: 9/26/2012
Accepted: 10/10/2012
Conflict-of-interest disclosure: The authors declare no competing financial interest

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